ArticlePloS one2020
Drug targeting CYP2E1 for the treatment of early-stage alcoholic steatohepatitis.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- The Role of Oxidative Stress in Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies.Nutrients · 2024Pooled it
- Polydatin ameliorates alcohol-induced gastric ulcer by inhibiting CASP3-mediated apoptosis.American journal of translational research · 2026Article
- Advances in the Pathogenesis of Metabolic Liver Disease-Related Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Review
- Article
- Synergistic Protective Effect of Fermented Schizandrae Fructus Pomace and Hoveniae Semen cum Fructus Extracts Mixture in the Ethanol-Induced Hepatotoxicity.Antioxidants (Basel, Switzerland) · 2023Article
- Identification of Cytochrome P450 2E1 as a Novel Target in Glioma and Development of Its Inhibitor as an Anti-Tumor Agent.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Article
- Dietary cholesterol in alcohol-associated liver disease.Immunometabolism (Cobham, Surrey) · 2023Review
- Amelioration of Hepatic Steatosis by the Androgen Receptor Inhibitor EPI-001 in Mice and Human Hepatic Cells Is Associated with the Inhibition of CYP2E1.International journal of molecular sciences · 2022Article
- Review
- β-Carotene Increases Activity of Cytochrome P450 2E1 during Ethanol Consumption.Antioxidants (Basel, Switzerland) · 2022Article
- Retinoids in the Pathogenesis and Treatment of Liver Diseases.Nutrients · 2022Review
- Vitamin Supplements as a Nutritional Strategy against Chronic Alcohol Consumption? An Updated Review.Antioxidants (Basel, Switzerland) · 2022Review
- Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease.International journal of molecular sciences · 2022Review
- Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis.Nutrients · 2021Article
- CYP2E1 in Alcoholic and Non-Alcoholic Liver Injury. Roles of ROS, Reactive Intermediates and Lipid Overload.International journal of molecular sciences · 2021Review
- ω-Imidazolyl-alkyl derivatives as new preclinical drug candidates for treating non-alcoholic steatohepatitis.Physiological reports · 2021Article
- Correction: Drug targeting CYP2E1 for the treatment of early-stage alcoholic steatohepatitis.PloS one · 2021Article
- A New CYP2E1 Inhibitor, 12-Imidazolyl-1-dodecanol, Represents a Potential Treatment for Hepatocellular Carcinoma.Canadian journal of gastroenterology & hepatology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsAlcoholic steatohepatitis (ASH)-the inflammation of fatty liver-is caused by chronic alcohol consumption and represents one of the leading chronic liver diseases in Western Countries. ASH can lead to organ dysfunction or progress to hepatocellular carcinoma (HCC). Long-term alcohol abstinence reduces this probability and is the prerequisite for liver transplantation-the only effective therapy option at present. Elevated enzymatic activity of cytochrome P450 2E1 (CYP2E1) is known to be critically responsible for the development of ASH due to excessively high levels of reactive oxygen species (ROS) during metabolization of ethanol. Up to now, no rational drug discovery process was successfully initiated to target CYP2E1 for the treatment of ASH.
methodsIn this study, we applied a rational drug design concept to develop drug candidates (NCE) including preclinical studies.
resultsA new class of drug candidates was generated successfully. Two of the most promising small compounds named 12-Imidazolyl-1-dodecanol (abbr.: I-ol) and 1-Imidazolyldodecane (abbr.: I-an) were selected at the end of this process of drug discovery and developability. These new ω-imidazolyl-alkyl derivatives act as strong chimeric CYP2E1 inhibitors at a nanomolar range. They restore redox balance, reduce inflammation process as well as the fat content in the liver and rescue the physiological liver architecture of rats consuming continuously a high amount of alcohol.
conclusionsDue to its oral application and therapeutic superiority over an off-label use of the hepatoprotector ursodeoxycholic acid (UDCA), this new class of inhibitors marks the first rational, pharmaceutical concept in long-term treatment of ASH.
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What OpenQuestion holds
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